This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to determine the structures of integral membrane proteins that cause multidrug resistance (MDR) in the treatment of cancer and infectious disease. We have obtained crystals from two classes of MDR transporters. The first class is from the Multiple Antimicrobial Toxin Extrusion (MATE) transport family. This family of bacterial MDR transporters confers resistance to antibiotics such as ciprofloxacin and the molecular structure is not known. The second class of membrane protein that we would like to determine is a mammalian MDR transporter from the ATP binding Cassette family. These transporters have an important role in the multidrug resistance to cancer chemotherapy. We have obtained diffracting crystals of both families of MDR transporters. In this proposal, we hope to use the beam lines at SSRL determine the structure of both of these transporters to further the understanding of the molecular basis of MDR.